Approved on.
Date of revision.
Pyrazinamide Tablets Instructions
Please read the instructions carefully and use under the guidance of your physician
[Drug Name].
Generic Name: Pyrazinamide Tablets
English Name: Pyrazinamide Tablets
Hanyu Pinyin: Biqinxian’an Pian
[Ingredients].
The main ingredient of this product is pyrazinamide.
Chemical name: pyrazinamide
Chemical structure formula.
Molecular formula: C5H5N3O
Molecular weight: 123.12
[Properties].
The product is white or off-white tablet (0.25g size); white or off-white unilateral scored tablet (0.5g size).
[Indications].
This product is only effective against Mycobacterium avium and is used in combination with other anti-tuberculosis drugs (such as streptomycin, isoniazid, rifampin and ethambutol) for the treatment of tuberculosis.
[Specifications
(1) 0.25g; (2) 0.5g.
[Dosage].
Orally. The usual dosage for adults, in combination with other anti-tuberculosis drugs, is 15-30 mg/kg daily in a single dose or 50-70 mg/kg twice or three times a week; up to 2 g daily for those taking it daily, up to 3 g each time for those taking it three times a week, and up to 4 g each time for those taking it twice a week.
[Adverse reactions
General Adverse Reactions
Fever, porphyria, and dysuria have been reported rarely. Gout (see [Precautions]).
Gastrointestinal reactions
The primary adverse reaction is hepatic (see WARNINGS). Hepatotoxicity is dose-related and can occur at any time during treatment. Gastrointestinal disturbances, including nausea, vomiting, and anorexia, have also been reported.
Blood and lymph
Thrombocytopenia and erythrocytic anemia with erythropoiesis, vacuolation of erythrocytes, and elevated serum iron concentrations rarely occur with this product. The pathogenesis of adverse coagulation reactions has also been rarely reported.
Other
Mild arthralgia and myalgia are frequently reported. Allergic reactions that have been reported include rash, urticaria, and pruritus. Fever, acne, photosensitivity, porphyria, dysuria, and interstitial nephritis have been reported infrequently.
[Contraindications
Pyrazinamide is contraindicated in the following groups:
– Severe hepatic injury.
-Sensitivity to this product.
-Severe gout.
[WARNING
Patients should have basal values of uric acid and liver function measured in serum before dosing. Patients who already have liver injury, or who are at high risk for pharmacogenic liver injury (eg, alcoholics) should be monitored closely.
Pyrazinamide should be discontinued when liver injury or increased uric acid associated with gouty joints occurs and should not be reintroduced.
[Caution].
General
Pyrazinamide inhibits renal excretion of uric acid, often resulting in asymptomatic hyperuricemia. Pyrazinamide should be discontinued when hyperuricemia is associated with acute gouty arthritis.
Pyrazinamide should be used with more caution in patients with a history of diabetes mellitus and can be more difficult for dosing management.
Resistance to pyrazinamide in Mycobacterium tuberculosis primaries is uncommon. If resistance is known or suspected to occur, in vitro ex vivo culture and susceptibility testing to pyrazinamide and commonly used first-line drugs is required. There is a lack of reliable in vitro pyrazinamide resistance testing methods. The above experiments need to be performed in validated laboratories.
Cross-sensitivity, patients with hypersensitivity to ethionamide, isoniazid, nicotinic acid, or other drugs with similar chemical structures may also be hypersensitive to this product.
Message to Patients
Patients should inform their doctor first if they have the following symptoms: fever, loss of appetite, lethargy, nausea and vomiting, dark yellow urine, yellowing of the skin and eyes, joint pain or swelling.
The treatment process requires that the dosing regimen must be followed, with special emphasis on no missed doses.
Laboratory testing
Basic liver function studies [specifically alanine aminotransferase ALT (SGPT) and glutamate aminotransferase AST (SGOT) tests] and uric acid levels should be performed prior to treatment. This product may increase alanine aminotransferase, portal aminotransferase, and blood uric acid concentration measurements. Appropriate laboratory testing should be performed periodically or if any clinical signs or symptoms develop during treatment.
Drug/Lab Test Interactions
Pyrazinamide has been reported to interfere with the urine ketone body test tablet ACETEST® and the urine ketone body assay KETOSTIX® resulting in a pink-brown color.
Carcinogenicity, Mutagenicity, Fertility Impairment
Bio-lifetime assays were performed in rats and mice after pyrazinamide was administered in the diet at concentrations up to 10,000 ppm. The estimated daily dose for mice was 2 g/kg, or 40 times the maximum human dose, and for rats was 0.5 g/kg, or 10 times the maximum human dose. Pyrazinamide was not carcinogenic in rats or male mice; no conclusions could be drawn for female mice because of the insufficient number of surviving control mice.
Pyrazinamide showed no mutagenic effect in the Ames bacterial test, but induced chromosomal aberrations in human lymphocyte cultures.
Pregnancy: teratogenic effects – PregnancyCclass
Animal reproduction studies have not been performed with pyrazinamide. It is also unclear whether pyrazinamide causes fetal damage when given to pregnant women or whether it affects reproductive capacity. Pyrazinamide should be given to pregnant women only when clearly needed.
[For Pregnant and Lactating Women
Pregnant patients with TB may be treated with isoniazid, rifampin, and ethambutol for 9 months and considered if they are resistant to any of these drugs and may be sensitive to this product. Small amounts of pyrazinamide have been found in breast milk. Therefore, given the risks and benefits of this treatment, caution is advised in the use of pyrazinamide in nursing mothers. This product is in FDA Pregnancy Drug Category C.
[Pediatric Use].
This product is highly toxic and should not be used in children. It should be used only after weighing the pros and cons.
[Geriatric use
Clinical studies of pyrazinamide did not include a sufficient number of patients 65 years of age and older to determine if they respond differently than younger patients. Other reports of clinical use have not identified differences in response between older and younger patients. In general, dose selection in older patients should be cautious, usually starting at the lower end of the dose range, due to the fact that older adults often have decreased hepatic or renal function, concomitant disease, or application of other medications.
Patients with impaired renal function do not require dose reduction. However, doses should be carefully selected at the low end of the dose range.
[Drug Interactions].
(1) Combination of this product with allopurinol, colchicine, probenecid, and sulfopiridone may increase blood uric acid concentrations and decrease the efficacy of these drugs in gout. Therefore, the dose should be adjusted when combined to control hyperuricemia and gout.
(2) When combined with ethionamide, the adverse effects may be enhanced.
(3) The blood concentration of cyclosporine may be reduced when used with pyrazinamide, so the blood concentration should be monitored and the dose adjusted accordingly.
[Drug overdose
Experience with overdose is limited. In one case report of an overdose, abnormal liver function tests were seen. Symptoms resolved after discontinuation of the drug. Clinical monitoring and supportive therapy should be used. Pyrazinamide can be removed by dialysis.
[Pharmacologic Toxicology].
It has a good antibacterial effect on human type Mycobacterium tuberculosis. It has the strongest bactericidal effect at pH 5-5.5 and is the best bactericidal drug available, especially for tuberculosis bacteria in phagocytic cells growing slowly in an acidic environment. It can kill Mycobacterium tuberculosis at a concentration of 12.5μg/ml and 50μg/ml in vivo. The intracellular inhibition concentration of Mycobacterium tuberculosis is 10 times lower than that of extracellular, and it has almost no inhibition effect in neutral and alkaline environment. The mechanism of action may be related to pyrazinic acid. Pyrazinamide penetrates into phagocytes and enters the body of Mycobacterium tuberculosis, and the amidase in the body of Mycobacterium tuberculosis causes the amide group to be removed and converted into pyrazinic acid to exert antibacterial effects. In addition, because pyrazinamide is similar to nicotinamide in chemical structure, it interferes with dehydrogenase by replacing nicotinamide and prevents dehydrogenation, preventing the use of oxygen by Mycobacterium tuberculosis, which affects the normal metabolism of the bacteria and causes death.
[Pharmacokinetics
Pyrazinamide is well absorbed in the gastrointestinal tract, with peak plasma concentrations reached within 2 hours. At doses of 20 to 25 mg/kg, plasma concentrations typically range from 30 to 50 μg/mL. pyrazinamide is widely distributed in body tissues and fluids, including the liver, lung, and cerebrospinal fluid (CSF). In patients with meningitis, CSF concentrations are nearly equal to steady-state plasma concentrations. The plasma protein binding of pyrazinamide is approximately 10%.
The half-life of pyrazinamide in patients with normal hepatic and renal function is 9 to 10 hours. The half-life may be prolonged in patients with hepatic or renal impairment. Pyrazinamide is hydrolyzed in the liver to pyrazinic acid, its main active ingredient. Pyrazinic acid is hydrolyzed to the major excretion, 5-hydroxypyrazinic acid.
About 70% of the oral dose of the drug is excreted in the urine, primarily through filtration by the internal glomerulus within 24 hours.
The inhibitory or bactericidal effect of pyrazinamide on Mycobacterium tuberculosis is dependent on the concentration at the site of infection. The mechanism of action is not clear. The drug is active in vivo and in vitro only at lower pH values.
[Storage].
Store under shade and seal.
[Packaging
Packaged in high-density polyethylene bottles for oral solids, 100 tablets/bottle.
[Expiration date
18 months
[Executive Standard
[Approval Number
State Drug Administration H19993002 (0.25g); State Drug Administration H******** (0.5g).
[Drug Marketing Authorization Holder
Name: Chongqing Huabang Pharmaceutical Co.
Registered Address: No. 69, Renhe Xingguang Avenue, Yubei District, Chongqing, China
Postal code: 401121
Telephone: 023-67034120 800-8070618 (need to use a landline to call)
Fax number: 023-67886970
[Manufacturer].
Company name: Chongqing Huabang Pharmaceutical Co.
Production Address: No. 69, Xingguang Avenue, Renhe, Yubei District, Chongqing
Postal code: 401121
Telephone: 023-67034120 800-8070618 (need to use a landline to call)
Fax number: 023-67886970
Website: http://www.huapont.cn